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O2 and femoral artery blood flow during heavy-intensity, knee-extension exercise
1Canadian Centre for Activity and Aging, 2School of Kinesiology, and 3Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada
Submitted 8 July 2004 ; accepted in final form 1 April 2005
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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O2) kinetics; however, there are limited data regarding the relationship of blood flow and O2 kinetics for heavy-intensity exercise. The purpose was to determine the exercise on-transient time course of femoral artery blood flow (
leg) in relation to O2 during heavy-intensity, single-leg, knee-extension exercise. Five young subjects performed five to eight repeats of heavy-intensity exercise with measures of breath-by-breath pulmonary O2 and Doppler ultrasound femoral artery mean blood velocity and vessel diameter. The phase 2 time frame for O2 and leg was isolated and fit with a monoexponent to characterize the amplitude and time course of the responses. Amplitude of the phase 3 response was also determined. The phase 2 time constant for O2 of 29.0 s and time constant for leg of 24.5 s were not different. The change (
) in O2 response to the end of phase 2 of 0.317 l/min was accompanied by a leg of 2.35 l/min, giving a leg-to-O2 ratio of 7.4. A slow-component O2 of 0.098 l/min was accompanied by a further leg increase of 0.72 l/min (leg-to-O2 ratio = 7.3). Thus the time course of leg was similar to that of muscle O2 (as measured by the phase 2 O2 kinetics), and throughout the on-transient the amplitude of the leg increase achieved (or exceeded) the leg-to-O2 ratio steady-state relationship (ratio 
4.9). Additionally, the O2 slow component was accompanied by a relatively large rise in leg, with the increased O2 delivery meeting the increased O2. Thus, in heavy-intensity, single-leg, knee-extension exercise, the amplitude and kinetics of blood flow to the exercising limb appear to be closely linked to the O2 kinetics. Doppler blood flow; muscle oxygen uptake; oxygen uptake slow component
O2) at exercise onset (O2 kinetics) might be limited by the rate of increase in blood flow and O2 delivery to the exercising muscle. In the moderate-intensity exercise domain, the relationship of the time course of blood flow vs. O2 increase has been assessed from various measures of blood flow. De Cort et al. (5) found that the time course [mean response times (MRTs)] of the adjustment of cardiac output (; measured by pulsed Doppler ultrasound) was faster than that of O2 in the transition from unloaded to moderate-intensity cycling exercise. Subsequently, Grassi et al. (12) measured leg blood flow (leg) using a constant infusion thermodilution technique, also in the transition from unloaded to moderate-intensity cycling exercise. They observed a "phase 1" of rapid increase in leg and an overall similar time course (MRTs) of leg, leg O2, and alveolar O2 of 35 s. Additionally, a number of investigators have now employed Doppler ultrasound, which allows continuous sampling of the mean blood velocity (MBV) in the feed artery to an exercising limb and thus estimation of the time course of the increase in blood flow to the exercising muscle group (6, 15, 28). Radegran and Saltin (28) noted that, with the onset of passive leg movement (from rest) and with the transient from passive movement to voluntary exercise, leg showed a very rapid initial rise (phase 1) followed by an exponential rise ("phase 2"). In light of the biphasic blood flow response, there was a considerable difference in the time course of leg expressed as a MRT vs. the time constant (
) of the exponential phase 2 rise. A number of studies have now examined how the limb blood flow (and thus O2 delivery) contributes to the rate of increase in the exercise O2 during exercise of moderate intensity (4, 20, 21, 32). Given the variety in the exercise formats of the leg studies [alternate-leg, knee extension (KE) and flexion, alternate-leg KE, and single-leg KE], and an apparent variability in the influence of the muscle pump (phase 1) in relation to initiating exercise from rest or from very light exercise, these data have shown mixed results in relation to the rate of increase in the blood flow (and thus O2 delivery) to the exercising muscle group vs. the time course of the phase 2 pulmonary O2 [representing the increase in leg O2 (2)]. Studies of Grassi et al. (9, 10) with in situ canine muscle electrically stimulated at 60–70% maximum O2 and adenosine-induced vasodilation found no effect on the muscle O2 consumption kinetics with increased blood flow before the onset of exercise (9), or with an improved diffusion gradient for oxygen delivery to the muscle (10). Nevertheless, with arm exercise during a condition of elevated mean arterial pressure, subjects who showed an elevated forearm blood flow also showed an elevated O2 during the exercise transient (26), suggesting that a greater arm blood flow at the exercise onset allowed an increased muscle O2 consumption (14).
To date, however, there exists a paucity of data regarding the blood flow response to exercise in the heavy domain and the relationship with the rate of increase of O2 in the exercise transient. It is possible that O2 delivery limits the rate of rise of O2 during heavy exercise. Studies of prior heavy exercise have reported a speeding of the overall rate of increase in O2 on a subsequent heavy exercise bout (8, 19, 33) and suggested that this may be consequent to an increased blood flow on the second bout, thus overcoming a blood flow limitation of the first heavy exercise without prior warm-up. At stimulation levels to induce peak exercise in the canine muscle, Grassi et al. (11) observed that muscle O2 consumption kinetics were facilitated by faster O2 delivery (increasing blood flow before the on-transient). In contrast, in humans, during the transition from passive movement to one-legged intense, exhaustive exercise (supine), Bangsbo et al. (2) reported a faster leg (with thermodilution; 50% response, 12 s) vs. muscle O2 consumption (25 s) response, but the analysis included the early phase of the muscle pump increase in blood flow, and the excess delivery of O2 was only within the first 15 s. With similar methods during intense exercise, Krustrup et al. (17) commented that O2 delivery exceeded the O2 as reflected in the relatively high femoral venous O2 content. Williamson et al. (38) found no effect of lower body positive pressure, presumably impeding muscle perfusion, on the O2 kinetics of heavy-intensity leg cycling, suggesting that, even in this situation, the rate of rise and magnitude of the blood flow were adequate. In contrast, in forearm exercise, studies of Doppler blood flow during heavy-intensity exercise have suggested an inadequate O2 supply (34) with limitations in blood flow restricting the adaptation of oxidative metabolism at the onset of heavy exercise (14, 18). Nevertheless, to our knowledge, there exist only very recent studies (7, 13) of the time course of blood flow in relation to O2 kinetics for leg exercise of heavy intensity.
Thus the purpose of this study was to determine the exercise on-transient time course of femoral artery blood flow (leg) in relation to that of O2 during heavy-intensity, single-leg KE exercise. leg and O2 profiles were obtained from five to eight repeats of the exercise protocol to establish an ensemble average with a high signal-to-noise ratio and confidence in the kinetic parameter estimates. It was hypothesized that the time constant () for leg would be similar to, or less than, the O2 and that the amplitude of leg during the on-transient would be similar to, or exceed, that achieved for the steady-state exercise leg-to-O2 ratio. Thus bulk blood flow would be closely associated to O2 kinetics, although an O2 delivery limitation related to regional distribution within the muscle and matching of the O2 delivery to metabolic regions of O2 utilization would not be discounted.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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Exercise protocols.
Initially, subjects performed a ramp (20–25 W/min) exercise test on an electromagnetically braked cycle ergometer (CE) (Lode, model H-300-R) for determination of peak O2 (O2 peak) (O2 peak CE). O2 peak CE was obtained from breath-by-breath gas exchange and was established as the highest 15-s O2 obtained at fatigue.
On a second day, subjects performed incremental single-leg KE exercise to fatigue (O2 peak KE). The KE ergometer was custom-built [see Bell et al. (4)] after that described by Andersen et al. (1). The KE exercise involved active quadriceps contraction against a resistance (set on CE), followed by passive return of the leg to the flexed position. The test consisted of 2 min of "loadless" exercise followed by 1 min at a resistance of 100–500 g (3–15 W), depending on subject size and fitness. Work rate was then increased every 1 or 1.5 min, to ensure that the test produced fatigue in 8–12 min. The subjects performed the KE exercise at a rate of 30 extensions/min, with timing established by a metronome. Fatigue was reached when subjects could no longer maintain the rate of 30 extensions/min, despite verbal encouragement. The O2 peak KE test provided data to estimate the appropriate heavy-intensity work rate.
The heavy-intensity work rate was calculated to elicit a O2 corresponding to 80% O2 peak KE. The protocol consisted of 6 min of loadless exercise followed by a 6-min step (square wave) of heavy-intensity exercise and a 6-min loadless recovery. Subjects performed five to eight repeats of the constant-load KE exercise repeated on different days. Measurements from the individual trials were averaged to improve the signal-to-noise ratio.
Measurement.
O2 was measured breath by breath. A bidirectional, low-resistance, low-dead space (90 ml) turbine and volume transducer (Alpha Technologies VMM-110) was used to measure inspired and expired airflow. The turbine was calibrated before each test with a 3-liter syringe. Respired gases were measured at the mouth and analyzed for fractional concentrations of O2, CO2, and N2 by a mass spectrometer (Perkin Elmer MGA-1100). The mass spectrometer was calibrated daily against precision-analyzed gas mixtures. The time delay (TD) for a square-wave bolus of gas to pass from the turbine to the analysis system was determined, and the gas concentrations were time aligned to match gas volumes. The analog signals from the mass spectrometer and turbine transducer were sampled at 50 Hz and stored on a computer for offline breath-by-breath computations and later analysis. Pulmonary O2 was calculated by using algorithms of Beaver et al. (3). Heart rate was monitored by using an ECG with the electrodes in a modified V5 configuration.
Femoral artery MBV was measured by using Doppler ultrasound (Vingmed CFM 750) utilizing a 7.5-MHz pulsed-wave sector probe. MBV was measured during at least four, and up to six, repetitions (of the 5–8 KE trials performed by each subject), and the data from all trials were ensemble averaged for an individual to yield a single response. The probe was positioned over the femoral artery distal to inguinal ligament, and the probe position was hand held by an investigator to optimize the auditory and visual cues of the MBV signal. The QRS complex of the ECG tracing was used to discern the beat-by-beat MBV waveforms. MBV was calculated by integrating the total area under the MBV profile for each beat. Arterial diameter images were recorded using the Vingmed CFM 750 during one trial for each subject. Measurements of the images for vessel diameter were made by two observers to ensure that no interobserver differences existed. Arterial diameter was measured every 2 min throughout the test. It was shown that arterial diameter did not change throughout the test, and thus a mean arterial diameter was taken for calculation of blood flow for each subject [arterial diameter mean across subjects was 8.82 mm (SD 1.30)]. Mean leg was calculated as leg = MBV·
r2 (where r is radius, and MBV is at any time for each subject).
Blood samples were obtained during one of the constant-load trials for measurement of blood lactate. The samples were taken from the dorsal vein of the hand, using a Teflon catheter (Angiocath, 21 gauge) and heparinized syringes (3 ml). The hand and forearm were heated with a warm heating pad and a heat lamp to arterialize the venous blood samples (22). Samples were taken at 3 and 6 min of loadless KE, 3 and 6 min of heavy exercise, and at 3 and 6 min of recovery. Samples were immediately put in an ice bath and then analyzed. Lactate concentrations (mmol/l) were determined by using a blood-gas-electrolyte analyzer (Nova Stat Profile 9 Plus gas-electrolyte analyzer, Nova Biomedical Canada). Calibration was performed before and throughout the analysis procedure.
Data analysis.
Breath-by-breath pulmonary O2 data were initially examined by using the model-fitting software of Origin 41, with the purpose of removing data points representing "noise." A preliminary fit was done for each square-wave trial, and data points lying outside a 99% confidence interval of the fit were removed. The O2 data then were interpolated to 1-s intervals, time-aligned, and ensemble-averaged for each subject. Beat-by-beat MBV data were edited manually by visual inspection to remove beats when the signal had been lost or very low signals were obtained. Next the data were interpolated to 2-s intervals (1 contraction cycle) and time aligned and ensemble averaged for each subject. The MBV data were fit in Origin, and points lying outside the 99% confidence interval of fit were removed. The data were averaged over an 8-s interval. The 8-s averaged data provide "smoothed" data with better signal-to-noise ratio for modeling and allowing detection of systematic changes in the fitting and model parameters on a point-by-point basis, thereby providing a better estimation of the true, underlying physiological response.
The O2 and MBV data were modeled to estimate the parameters of the response using a monoexponential model as follows:
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O2 or MBV at time t, A0 is the baseline O2 or MBV, A is the asymptotic value to which O2 or MBV is assumed to project, is the time constant of the response, and TD is the time delay. The model-fitting strategy used (29) was designed to identify the phase 2 component (for O2 for our purposes). For the O2 data, initially a fitting window from 30 s after exercise onset (eliminating phase 1) to end exercise (6 min) was used. The window was then iteratively extended back toward the exercise onset (i.e., t = 0) until the "goodness of the fit" deteriorated, determined by three factors: 1) the flatness of the residual plot and deviations from the zero line; 2) a sudden increase in the 
2 value; and 3) a sudden increase in the value of as data from phase 1 were included in the fitting window. The phase 1-phase 2 transition was taken as that time point just before the time where these sudden changes occurred. Once the start point of phase 2 was determined, it was then used to fit to 60 s, and the window was then again lengthened (toward end exercise). The determinants mentioned above were again used, in this case to determine when the slow component began (phase 3).
The magnitude of the phase 1 plus phase 2 amplitude (A1 + A2) was determined from the O2 at the end of loadless to the end of phase 2 of the exercise O2. The amplitude of the phase 3 or slow component (A3) was calculated as the change () in O2 between the end of phase 2 (determined by fitting of O2) and end of exercise. Amplitude values were taken from values obtained from the fit at the required time points. The total amplitude was the O2 from loadless to the end of exercise at 6 min. The end-exercise averages were taken from three data points (i.e., 24 s).
The MBV data were fit for each subject using the same procedures as for the O2 data to identify from the fitting the occurrence of a phase 1 (muscle pump), phase 2, and phase 3. The amplitude of the total response for each was obtained from the MBV at loadless to end exercise. Absolute mean blood flow measurements (leg) were calculated for each individual from their measured vessel diameter and the MBV at the given time point.
Statistics.
Data are expressed as means and SD. The time courses of responses of O2 and MBV were compared by using a paired t-test, and their relationship was tested by Pearson product-moment correlation. The level of significance was set at P < 0.05.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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O2 peak CE was 3.69 l/min (SD 1.09) [47.5 ml·kg–1·min–1 (SD 7.2)], and O2 peak KE was 1.10 l/min [at a work rate of 30.0 W (SD 8.7)]. For the step transitions into heavy exercise, the work rate of 21.9 W (SD 3.3) elicited an end-exercise (6 min) O2 of 0.892 l/min (SD 0.218) or 80.4% (SD 6.1) of the O2 peak of the single-leg KE exercise. This work rate was in the heavy-intensity domain as characterized by a significant increase in blood lactate [from 1.28 (SD 0.59) to 3.66 mmol/l (SD 0.30)] and an identifiable slow component of the O2 response (see below).
Figure 1A shows 8-s averaged data for O2 with the phase 2 model best fit line and residuals for a representative subject, and Fig. 1B shows the MBV response and model fitting. The O2 and MBV on-transient kinetic parameter estimates for the step from loadless to heavy-intensity, single-leg KE exercise are given in Table 1.
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O2 was 0.478 l/min, and calculated leg was 1.55 l/min (Table 1). For the group, the phase 2 O2 response was modeled between 26 and 98 s after the onset of the transition from loadless to heavy exercise. The O2 amplitude from loadless exercise to the end of phase 2 was 0.317 l/min, with a phase 2 O2 of 29 s (Table 1), estimated with a 95% confidence interval [see Rossiter et al. (29)] averaging 2 s.
For the MBV, to allow for the possibility of a muscle pump effect over the first few contractions (at 30 rpm, a 2-s period for the KE and passive flexion cycle), the model fitting started at 8 s after exercise onset (i.e., representing data from 4 to 12 s) and extended to 118 s. The amplitude of the leg increase was 2.35 l/min. The MBV was 25 s (Table 1), estimated with a 95% confidence of 3 s. The O2 and MBV were not different and were not correlated (Fig. 2). The increase in leg was 7.4 l/min per the liter per minute increase in O2 (i.e., 2.35/0.317).
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O2 was evident in all subjects, averaging 0.098 l/min (Table 1), from the end of phase 2 (at 98 s) to end exercise at 6 min. A continuing increase in MBV also was evident in all subjects with a mean increase from the end of phase 2 of 23 cm/s, or 0.72 l/min (Table 1). This "slow-component" increase of leg was identified from the modeling procedures to start at 118 s after the exercise onset. This increase in leg was 7.3 l/min per the liter per minute increase in O2 (i.e., 0.72/0.098).
At end exercise, the O2 was 0.892 l/min with a leg of 4.62 l/min (Table 1). The total O2 amplitude of the exercise response of 0.414 l/min was met by a leg amplitude of 3.08 l/min, or an increase in blood flow of 7.4 l/min per liters per minute of O2.
The off-transient O2 kinetics, analyzed with a monoexponent (started 20 s postexercise) exhibited a O2 of 36 s (SD 4), which was not significantly greater than the on-transient O2 (29 s, P = 0.111). At the transition from heavy exercise to the loadless recovery, the leg was elevated above the 6-min end-exercise value (see Fig. 1B) by 0.78 l/min (averaged over the first 3 data points, or 24 s of recovery). Thereafter, the leg showed an exponential-like decline but remained above the end-exercise level for an average of 54 s (7 averaged data points); the of the decline was in the order of 2–3 min, such that, after 6 min of loadless exercise recovery, leg was still >20% above the prior loadless exercise value.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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O2 (29 s) and leg (25 s) were not different; 2) the amplitude of the increase in leg was 7.4 l/min per the liter per minute increase in O2; 3) the phase 3 slow-component O2 increase was accompanied by a "slow-component-like" response in leg with a leg-to-O2 of 7.3 l/min per liters per minute of O2; and 4) the off-transient leg response (, 2–3 min) was appreciably slower than the O2 off-kinetics (, 36 s).
The time course and amplitude data of the leg and O2 (representing increased muscle O2 consumption) allowed calculation of O2 delivery compared with O2 utilization throughout the exercise. The mean model parameters of the leg and O2 responses were used to generate Fig. 3. The time course of the exponential increase in leg (i.e., modeling the phase 2 alone) was similar ( = 25 s) to the time course of the increase in muscle metabolism as measured by the phase 2 O2 kinetics ( = 29 s), (Fig. 3A). The phase 2 increase in leg above loadless movement (i.e., leg amplitude, 2.35 l/min for a O2 increase of 317 ml/min) was 7.4 l/min blood flow per liters per minute of O2 (Fig. 3B), which was identical to the leg-O2 regression equation of Proctor et al. (27) for the steady-state response during cycling exercise in young untrained men. Given a whole body -to-O2 regression of a 5 l/min increase in per the liter per minute increase in O2 [i.e., = 5 O2 + 5; Whipp et al. (37)], the observed increase in leg is consistent with an additional blood flow redistribution to the exercising limb (23, 30). Importantly, throughout the transient, the leg-to-O2 was similar to (or exceeded) the steady-state relationship (Fig. 3B), implying that the increase in blood flow was closely associated with the increase of O2 throughout the exercise transient. Indeed, the estimated phase 2 increment in leg O2 delivery of 447 ml O2/min (Fig. 3C) [i.e., leg (2.35 l/min) x arterial O2 content (assumed 190 ml O2/l)] exceeded the increase in O2 (317 ml/min) by 40%. This O2 delivery-to-O2 ratio may be underestimated, as pulmonary O2 overestimates the "leg" O2 (12) (pulmonary O2 includes the O2 of ventilatory muscles and heart work, as well as possible O2 cost of stabilizing muscle groups). Nevertheless, with the assumption that the phase 2 pulmonary O2 reflected the increase in muscle O2 with exercise, given the leg data and estimate of O2 delivery, the increase of O2 could be met in the steady state by a modest O2 extraction of 70% across the exercising limb or an arteriovenous O2 difference (a-vDO2) of 135 ml/l. Given that the pulmonary O2 overestimates the muscle O2, this estimated a-vDO2 would be an overestimate. Proctor et al. (27) observed a leg a-vDO2 of 135 ml/l, or 65%, in light cycling exercise with no further increase at heavier work rates, although peak values in intense KE exercise of 155 ml/l have been observed (17). The venous O2 return (leg x venous O2 content), calculated from the model parameters as O2 delivery (leg x arterial O2 content) minus leg O2 (estimated as O2) actually showed an early rise over the first 45–60 s of exercise (Fig. 3C). Previously, Bangsbo et al. (2) and Krustrup et al. (17) reported an "excess" O2 delivery to the thigh muscle for the O2 requirement during the onset, up to 15–30 s, of intense exercise. Thus, in the present study, in heavy-intensity exercise, the increase in leg throughout the phase 2 on-transient was sufficient relative to the steady-state leg-to-O2 ratio. The leg during the exercise transient appeared closely related to the O2 kinetics (and thus muscle O2 consumption kinetics, which have a similar time course; Ref. 12), although we cannot discount a possible limitation in blood flow and O2 delivery distribution, beyond the femoral artery, within the exercising limb. The amplitude of the blood flow at the feed artery may be large enough to compensate for a lack of precise matching of local perfusion to areas of low metabolism.
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leg and O2 was not different, and O2 delivery matched (or exceeded) the O2 requirement (i.e., leg-to-O2 ratio exceeds the leg-to-O2 ratio when steady state is achieved). However, while the kinetics of blood flow were, on average, similar to O2 kinetics, there was variability among the subjects, with two of the five subjects showing slower blood flow kinetics (Fig. 2); however, the occurrence (in these two subjects) of slower leg kinetics appeared not to affect (i.e., appreciably slow) O2 kinetics. The amplitude of the blood flow increase relative to the O2 requirement is also important. For example, even in the subject with a leg of 34 s and O2 of 17 s, at 34 s into the transient the leg-to-O2 ratio of 3.8 (calculated from this individual's data) suggests that, in the transient, the blood flow delivery, at least to the limb, was only slightly below the leg-to-O2 ratio of the steady state (for this subject, 4.1). Given that leg can be twice as long as the O2, this suggests that the time course data alone (without also considering the amplitude changes) are insensitive to interpreting data as an O2 limitation or not.
The Doppler blood flow measures during heavy-intensity KE exercise in the present study appear accurate in relation to the measures of others and to the -O2 relationship reported for exercise and for the redistribution of blood flow to exercising muscle. At loadless exercise, at a O2 of 0.5 l/min, the leg was 1.6 l/min. Saltin et al. (31) measured (with Doppler) a passive exercise blood flow of 1.2 l/min, and Bangsbo et al. (2) and Krustrup et al. (17), using thermodilution, measured passive KE exercise flows in the thigh of 1.8 and 2.0 l/min, respectively. The phase 2 heavy-intensity leg of 3.9 l/min was similar to the values of Radegran and Saltin (28) for a similar work rate. At the end-exercise O2 of 0.9 l/min, leg was 4.6 l/min. For a similar O2 in one-leg KE exercise, Krustrup et al. (17) reported a thigh blood flow of 4.3 l/min. MacDonald et al. (21) (with Doppler) measured a leg of 3.7 l/min in alternate-leg KE and flexion exercise with a O2 of 1.2 l/min or an increase of O2 of 450 ml·min–1·leg–1 (similar to the present study). The magnitude of the increase in blood flow, for this increase of O2, was similar to our data (MacDonald et al., 3.3 l/min; present data, 3.1 l/min). In supine bilateral KE exercise, the data of Fukuba et al. (7) (using Doppler) showed a two-leg leg of 3.7 l/min for a O2 of 0.71 l/min, comparable to the present phase 2 leg of 3.9 l/min at O2 of 0.79 l/min. Proctor et al. (27) from thermodilution measures during the steady state of cycling at increasing work rates in young men found a regression equation of leg = 7.5 leg O2 – 0.03. For our phase 2 increase of 0.317 l/min, this would estimate a leg increase of 2.34 l/min, equivalent to our value of 2.35. Similarly, for the total O2 amplitude of 0.414 l/min, the estimated leg of 3.07 l/min compares with our value of 3.08 l/min. Thus the consistency of the leg measures lends confidence to the validity of the blood flow data of the exercise transient.
A number of previous studies have examined the time course of leg (and thus O2 delivery) in the on-transient of exercise (usually moderate intensity) vs. the time course of the increase in O2 (4, 12, 20, 21, 32). A confounding factor in comparison of the rate of increase in blood flow vs. O2, however, relates to whether the exercise is initiated from rest, passive movement, or a prior exercise condition. Early studies using the Doppler technique used supine light-intensity exercise of 2-s leg-lifts and noted very rapid increases in the blood velocity (35). In the transition from rest to passive movement and then active exercise (28), or from rest to exercise (20, 32), there is a very rapid initial increase of blood flow to the exercising limbs attributed to the muscle pump. With passive movement to exercise transitions, fully 50% of the total increase in moderate exercise blood flow was achieved by 4.5–8.5 s (28) or by 12 s (or less) of intense exercise (2). This initial "surge" in blood flow was followed by an exponential increase [phase 2; Radegran and Saltin (28)]. Thus the time course for the increase in blood flow determined from the exercise start to the steady-state using the MRT will consist of a rapid and then slower blood flow increase, whereas the time course determined after the initial few contractions (i.e., in the exponential phase as given by the phase 2 ) should include only the slower increase in blood flow. The data of MacDonald et al. (20), with a rest-to-light-exercise transient, showed a rapid MRT of 17 s, but a phase 2 leg of 37 s (greater than the O2 of 23 s). Radegran and Saltin (28) noted a progressive increase in MRT for transitions from passive exercise to 10, 30, 50, and 70 W of 4, 21, 41, and 45 s, respectively, whereas this was not the case for the leg. Thus there was a lesser relative contribution of the muscle pump to the total increase of blood flow as exercise intensity was increased. It appears the muscle pump provides a rapid increase in blood flow not reflected in an abrupt "jump" in O2 (12) and presumably beyond the requirement for O2 delivery at the onset (first 15 s) of exercise (2). Thus the leg (phase 2) is the appropriate analysis for determination of the relationship of blood flow to O2 (or muscle O2 consumption).
The leg is the rate of the continued increase in blood flow in relation to the exponential rise of the O2. In the present study, heavy-intensity KE exercise was undertaken from a baseline of loadless KE (estimated at 3 W). A substantial muscle pump effect was not observed. MBV at 8 s following exercise onset (i.e., 8-s averaged data, or the mean of data from 4 to 12 s) showed a rise from baseline MBV to this first point by 21 cm/s, or 28% of the total A1 and A2 of 76 cm/s. This initial rise over 8 s is in close proportion to that expected with a leg (63% response) of 25 s, and thus the protocol eliminated any large, rapid muscle pump increase in limb blood flow. Nevertheless, the phase 2 kinetics of the blood flow response were isolated by the modeling technique. The kinetics yielded a leg of 25 s, similar to the phase 2 O2 of 29 s. Most previous studies have used moderate-intensity exercise. Shoemaker et al. (32) studied the rest-to-exercise transient during moderate-intensity, alternate-leg KE and knee flexion. The phase 2 MBV on-transient was 35 s, which was considerably faster than the O2 of 72 s. However, the O2 of the subjects during the leg exercise was very different from their O2 for cycling exercise of 18 s, perhaps because the exercise required muscle contraction during both KE and knee flexion in lifting and lowering a weight, and it was noted that the sustained muscular tension might restrict inflow of blood (amplitude of the response) to the active muscle (32). MacDonald et al. (20) found a MRT of leg of 17 s vs. a O2 MRT of 29 s; however, the phase 2 was 40 s vs. 23 s for O2. Our laboratory (4) previously reported fast MBV kinetics (i.e., = 20 s) vs. O2 kinetics 100 s in a loadless to moderate (or perhaps heavy-intensity domain) KE exercise transition in older men. MacDonald et al. (21) reported a leg of 18 s with a phase 2 O2 of 26 s for leg extension/flexion exercise. In that study, for at least some subjects, the exercise appeared to be in the heavy-intensity exercise domain, and the results show a similar relationship of the leg and O2 as in the present study. Fukuba et al. (7) have now reported for supine bilateral KE a leg of 41 s with a phase 2 O2 of 49 s. Thus, during the phase 2 on-transient of moderate- or heavy-intensity exercise, the time course of the leg increase often has been reported to be somewhat faster than the O2 response, although the present data showing that the time course for the blood flow and O2 of heavy-intensity exercise were not different, but closely related, agree with the data of Grassi et al. (12) for moderate-intensity exercise.
Limited data are available to quantify the leg response during the phase 3 O2 slow component of heavy-intensity exercise. The O2 slow component was evident in all subjects, with a TD to the appearance of the slow component of 98 s and amplitude of 100 ml/min (to end exercise at 6 min) and was accompanied by a progressive increase of leg with a TD of 118 s and amplitude of 720 ml/min (Fig. 3A). Of importance, compared with the data of Fukuba et al. (7), we showed a clear increase in blood flow, whereas they did not report a slow component-like response for blood flow but rather a blood flow adaptation that reached a steady-state very early in the exercise transition. The data of Fukuba et al. (7) in supine bilateral KE showed a O2 slow component of 78 ml/min (at a lower relative intensity than the present study) but with no evidence of a blood flow slow component (or at least a rather small increase of 40 ml·min–1·leg–1). The heavy-intensity exercise data of Hughson et al. (13) show an increased blood flow accompanying the O2 slow component, although the magnitude of the phase 3 blood flow was not quantified. In earlier studies, Radegran and Saltin (28) noted in two subjects exercising at 75% O2 peak a phase 3 of blood flow. MacDonald et al. (21) observed a O2 slow component in four of six subjects, and in three of these a three-component exponential model described a phase 3 slow component-like leg response. As in our results, their modeling yielded a slightly longer TD of the phase 3 blood flow response (146 s) compared with the TD of the O2 slow component response (131 s). The amplitude of our phase 3 leg to O2 was 7.3 (l/min per l/min) (Fig. 3B), and this change in blood flow per O2 was almost identical to that observed during phase 2 of the exercise response (leg/O2 = 7.4). In the data of MacDonald et al. (21), the A3 of O2 was 140 ml/min with a 435 ml/min leg increase (ratio 3.1); however, this included one subject who showed no phase 3 leg increase. Krustrup et al. (17) found that O2 extraction plateaued at 140 ml/l early (30 s) during intense exercise, whereas leg O2 continued to rise by 300–600 ml/min over the subsequent 3 min. Similarly, in the present study, the O2 slow component appeared to be accommodated mainly by an increase in blood flow (O2 delivery) without a greater O2 extraction or deoxygenation (Fig. 3C). Similarly, Hughson et al. (13) observed an increase of blood flow to the exercising limb during the period corresponding to the O2 slow component. It is suggested from the present data that the phase 3 leg response is of a delayed nature [initiated or "evolving" some time after the onset of the exercise, as for the O2 slow component; Paterson and Whipp (25)]. The "onset" of the phase 3 increase of leg (as well as it could be determined from the model fitting) occurred with the estimated TD 20 s after that for the O2 response. Thus our data may suggest a link between the mechanisms regulating the O2 utilization and O2 delivery in the phase 3 period of the slow component of O2. However, with the total O2 slow component of 100 ml/min over the 4-min period (and very slow kinetics of the slow component), the increase in O2 over the 20-s period before the leg showed that an increase would only amount to 5 ml/min. Although others have noted that this phase 3 increase in leg follows after the O2 slow component, given the limitations in precision in determining the start point of the phase 3, and given the very small amplitude of the increase in O2 over this 20-s period, we do not feel confident in making a substantive conclusion on whether the O2 precedes or coincides with the leg in phase 3. The mechanisms controlling the blood flow increase may represent a continuation of those acting in phase 2 (and meeting the O2 requirement) or additional factors such as the accumulating lactate or a vasodilatory substance such as adenosine (31) or might be related to additional fiber recruitment of lower efficiency fast-twitch motor units (36). The cause of the O2 slow component remains a topic of debate, and, until this is resolved, it is difficult to speculate on the mechanisms of an accompanying increase in leg.
With the return to loadless exercise, the O2 off-kinetics [36 s (SD 4)] were similar (P = 0.11) to the phase 2 O2 on-kinetics, although in the direction of slower off-kinetics from heavy-intensity exercise as reported by Ozyener et al. (24). leg showed an initial hyperemia of 0.8 l/min above the end-exercise leg [to 5.40 l/min (SD 0.66)] and remained above the end-exercise level for 1 min. The decline in MBV showed a very long , ranging from 1.5 to 6 min. A slightly slower off-transient leg vs. O2 was noted by Hussain et al. (15) following moderate-intensity exercise, and following severe exercise there was a very long time course of the leg decline (16). Additionally, Yoshida and Whipp (39) have reported a slower (compared with O2) in the off-transient. Thus the O2 off-kinetics were faster than the reduction in blood flow.
In summary, the time course and amplitude of femoral artery blood flow during the exercise on-transient of heavy-intensity, single-leg KE exercise appeared to be closely associated with the muscle O2 consumption kinetics (measured as the pulmonary O2). Thus throughout the heavy-intensity exercise transient, the amplitude of the blood flow for a given O2 met the blood flow-to-O2 ratio achieved in the exercise steady state. With this heavy-intensity exercise, the observed O2 slow component was accompanied by a steadily increasing leg with the estimated increase in O2 delivery meeting the increasing O2 requirement.
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O2 during repeated bouts of heavy knee extension exercise in humans. Exp Physiol 89: 243–253, 2004.O2 on-kinetics in isolated in situ canine muscle. J Appl Physiol 85: 1394–1403, 1998.O2 on-kinetics in isolated in situ canine muscle. J Appl Physiol 85: 1404–1412, 1998.O2 on-kinetics in canine muscle contracting at peak O2. J Appl Physiol 89: 1293–1301, 2000.O2 on blood flow dynamics at onset of forearm exercise. J Appl Physiol 81: 1619–1626, 1996.O2 kinetics in heavy submaximal exercise by hyperoxia and prior high-intensity exercise. J Appl Physiol 83: 1318–1325, 1997.
